Association of TNF-\u03b1 -308G\u2009>\u2009A polymorphism with susceptibility to tendinopathy in athletes: a case\u2013control study

Lucas Rafael Lopes,João Alves Grangeiro Neto,João Antonio Matheus Guimarães,Vitor Almeida Ribeiro De Miranda,Gabriel Garcez De Araujo Souza,Rodrigo De Araújo Goes,Victor Soares Wainchtock,Jamila Alessandra Perini

doi:10.1186/s13102-021-00276-2

Abstract

BackgroundHigh levels of the tumor necrosis factor alpha (TNF-α) induce apoptosis and pro-inflammatory effects for primary degeneration of tendon and development of tendinopathy. The aim of this study was to investigate the association between the TNF-α polymorphisms and tendinopathy in athletes.MethodsTwo hundred and seventy athletes (135 tendinopathy cases and 135 controls) were included and genotyped (TNF-α -1031T > C; -857 C > T; -308G > A) using TaqMan validated assays. The association of the polymorphisms with tendinopathy was evaluated by a multivariate logistic regression model, using odds ratios (OR) and 95 % confidence intervals (CI).ResultsThe variant allele − 308 A was significantly associated with patellar (OR: 1.9; 95 % CI: 1.01–3.6) or Achilles tendinopathies (OR: 2.7; 95 % CI: 1.1–6.7). No significant differences were found in allele or genotype distributions of the − 1031T > C and − 857 C > T polymorphisms between cases and controls. TNF-α TCA haplotype was associated with increased tendinopathies risk, either considering all cases (OR: 2.6, 95 % CI: 1.3–5.3), patellar (OR: 3.3, 95 % CI: 1.5–7.3), rotator cuff (OR: 3.1, 95 % CI: 1.4–7.2) or Achilles tendinopathies (OR: 3.8, 95 % CI: 1.1–12.7).ConclusionsThese results suggest that the TNF-α polymorphisms could influence the susceptibility to developing tendinopathy among athletes. Knowledge of the TNF-α polymorphisms associated to tendinopathy in athletes can further understanding of the inflammatory role in the early stages of the disease and contribute for sports injury surveillance programmes, in which athletes with TNF-α TCA haplotype could be early subjected to cryotherapy after training and competition to avoid tendinopathy development.

Highlights

High levels of the tumor necrosis factor alpha (TNF-α) induce apoptosis and pro-inflammatory effects for primary degeneration of tendon and development of tendinopathy
An experimental tendinopathy model produced by overuse shown that Tumor necrosis factor alpha (TNF-α) Messenger RNA (mRNA) was increased 11-fold in torn supraspinatus tendon compared to controls [11]
There was no significant difference of the age, sex and sports modality between tendinopathies subgroups and control; these variables entered the multivariate model for stratified association analyzes, according to the biological importance for the tendinopathy development

Summary

Introduction

High levels of the tumor necrosis factor alpha (TNF-α) induce apoptosis and pro-inflammatory effects for primary degeneration of tendon and development of tendinopathy. Tendinopathy is characterized by pain, swelling, structural change and functional limitation of the tendon due to overuse [1, 2]. It is the main reason for clinical musculoskeletal complaint in athletes (15–50 %) [3], which can lead to reduced level of performance or end of one’s sport career [4]. Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), and growth factors have been implicated as a mechanism in early stages of tendinopathies [1, 9]. TNFα and its receptors were expressed in peritendinous tissue [12], and in rounded/enlarged nucleus human tenocytes, a typical characteristic of tendinopathy [13]

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